Elevated ventricular filling pressures ultimately result in systemic and pulmonary venous congestion and edema, and are thus largely responsible for the manifestations of congestive heart failure. The goal of this research proposal is to assess the role of incomplete myocardial relaxation and ventricular viscoelastic properties in the development of elevated ventricular filling pressures. In particular, the applicant purposes: (a) to refine and assess in detail, methodology relating to the detection of incomplete myocardial relaxation in man, (b) to pursue recent observations made by the applicant and his co-workers that under certain circumstances incomplete myocardial relaxation may be pharmacologically reversible, and (c) to determine whether, and to what extent filling rate and volume history are important determinants of ventricular diastolic pressure. To achieve these aims, both animal and clinical investigations are planned. In the clinical studies, it is proposed to assess methodology relating to the detection of incomplete myocardial relaxation in normal and diseased human hearts, and in particular to study (a) the rate of fall of left ventricular wall stress (negative d sigma/dt) including fiber corrected stress; (b) the time course of LV pressure decline during isovolumic relaxation, and the T1/2 of this time course, and (c) peak negative dP/dt and the rate of circumferential fiber lengthening in early diastole (V cfl). Studies are planned in instrumented dogs where LV pressure-diameter and wall force-myocardial segment length relations will be assessed in relation to interventions designed to induce, and then correct, incomplete myocardial relaxation. Finally, a series of studies is proposed to learn: (a) in conditions of LV volume overload and high diastolic inflow rate (e.g. aortic regurgitation) is the left ventricle protected against high diastolic pressures by the occurence of significant viscous "creep"?, (b) is hysteresis an important property of the left ventricle?, and (c) is the recent volume history of the left ventricle an important determinant of its subsequent diastolic pressure relation?